Study to Evaluate the Efficacy and Safety of Selonsertib in Participants With Moderate to Advanced Diabetic Kidney Disease (MOSAIC)

MOSAIC - A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study Evaluating the Efficacy and Safety of Selonsertib in Subjects With Moderate to Advanced Diabetic Kidney Disease

The primary objective of this study is to evaluate whether selonsertib (SEL) can slow the decline in kidney function in participants with moderate to advanced diabetic kidney disease (DKD).

Study Overview

• Status: Completed
• Conditions: Diabetic Kidney Disease
• Intervention / Treatment: Drug: Placebo; Drug: SEL

Detailed Description

Following the screening period, eligible participants will enroll into a Run-in period of at least 5 weeks and receive placebo to match SEL for at least 1 week and then SEL for at least 4 weeks. After completing Run-in period, eligible participants will be randomized and receive either SEL or placebo to match SEL for at least 48 weeks.

• Study Type: Interventional
• Enrollment (Actual): 384
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Fitzroy, Australia, 3065
    • St. Vincent Hospital, Melbourne
  • Parkville, Australia, 3052
    • Royal Melbourne Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3081
      • Austin Health and University of Melbourne
• Canada
  • Barrie, Canada, L4M 7G1
    • LMC Clinical Research Inc. (Barrie)
  • Brampton, Canada, L6S 0C6
    • LMC Clinical Research Inc. (Brampton)
  • Concord, Canada, L4K 4M2
    • LMC Clinical Research Inc. (Thornhill)
  • Etobicoke, Canada, M9R 4E1
    • LMC Clinical Research Inc. (Etobicoke)
  • Kitchener, Canada, N2H 5Z8
    • Clinical Research Solution Inc.
  • Laval, Canada, H7T 2P5
    • Centre de Recherche Clinique de Lava
  • Vancouver, Canada, V5Y 3W2
    • Dr TGElliott Inc dba BC Diabetes
  • Winnipeg, Canada, R3C 0N2
    • Winnipeg Clinic
• Japan
  • Asahikawa, Japan, 078-8510
    • Asahikawa Medical University Hospital
  • Chiba, Japan, 260-0801
    • National Hospital Organization Chiba-East-Hospital
  • Kagoshima, Japan, 890-8520
    • Kagoshima University Hospital
  • Kitakyushu-shi, Japan, 802-8555
    • Kokura Memorial Hospital
  • Kofu, Japan, 400-0027
    • Yamanashi Prefectural Central Hospital
  • Kurobe-shi, Japan, 938-8502
    • Kurobe City Hospital
  • Kurume-shi, Japan, 830-0011
    • Kurume University Hospital
  • Mito-shi, Japan, 310-0826
    • Nakamoto Medical Clinic
  • Mito-shi, Japan, 310-0845
    • Kozawa Eye Hospital And Diabetes Center
  • Musashino, Japan, 180-8610
    • Japanese Red Cross Musashino Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagoya-shi, Japan, 455-8530
    • Japan Organization of Occupational Health and Safety Chubu Rosai Hospital
  • Nagoya-shi, Japan, 457-8511
    • Daido Clinic
  • Naka-shi, Japan, 311-0113
    • Nakakinen Clinic
  • Niigata, Japan, 9518520
    • Niigata University Medical & Dental Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Japan, 558-8558
    • Osaka General Medical Center
  • Saitama-shi, Japan, 338-0837
    • Hoshina Clinic
  • Sanuki-shi, Japan, 769-2393
    • Sanuki Municipal Hospital
  • Tachikawa-shi, Japan, 190-8531
    • Tachikawa Hospital
  • Tokyo, Japan, 173-8610
    • Nihon University Itabashi Hospital
  • Tokyo, Japan, 153-0051
    • Mishuku Hospital
  • Toyota-shi, Japan, 471-8513
    • Toyota Memorial Hospital
  • Yokohama-shi, Japan, 236-0004
    • Yokohama City University Hospital
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital (Auckland District Health Board)
  • Auckland, New Zealand
    • Middlemore Clinical Trials Trust trading as Middlemore Clinical Trials
  • Christchurch, New Zealand, 8011
    • Lipid and Diabetes Research Group
  • North Shore, New Zealand, 622
    • Waitemata District Health Board- North Shore Hospital
  • Wellington, New Zealand, 6021
    • Endocrine, Diabetes & Research Centre (Capital and Coast District Health Board)
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Kidney Disease and Hypertension Centers
    • Tucson, Arizona, United States, 85712
      • AKDHC Medical Research Services, LLC
  • California
    • Canyon Country, California, United States, 91350
      • Clearview Medical Research, LLC
    • Glendale, California, United States, 91206
      • Kidney Disease Medical Group, Inc.
    • Granada Hills, California, United States, 91344
      • Renal Consultants Medical Group
    • Greenbrae, California, United States, 94904
      • Marin Endocrine Care & Research, Inc.
    • La Mesa, California, United States, 91942-3059
      • California Institute of Renal Research
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Newport Beach, California, United States, 92663
      • Rose Salter Medical Research Foundation
    • Northridge, California, United States, 91324
      • Valley Renal Medical Group Research
    • San Diego, California, United States, 92123
      • California Institute of Renal Research
    • San Dimas, California, United States, 91773
      • California Kidney Specialist
  • Colorado
    • Denver, Colorado, United States, 80246
      • Creekside Endocrine Associates, PC
    • Golden, Colorado, United States, 80401
      • New West Physicians, Inc
    • Westminster, Colorado, United States, 80031
      • Western Nephrology and Metabolic Bone Disease, PC
  • Florida
    • DeBary, Florida, United States, 32713
      • Omega Research Maitland, LLC
    • Lauderdale Lakes, Florida, United States, 33313
      • South Florida Research Institute
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Ocala, Florida, United States, 34471
      • Discovery Medical Research Group, Inc
    • Port Charlotte, Florida, United States, 33952
      • Coastal Nephrology Associates Research Center, LLC. D/B/A Volunteer Medical Research
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Center for Clinical Research
    • Lawrenceville, Georgia, United States, 30046
      • Georgia Nephrology Research Institute
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Boise Kidney & Hypertension, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research by Design, LLC
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Buynak Clinical Research, P.C.
  • Iowa
    • Council Bluffs, Iowa, United States, 51501
      • West Broadway Clinic
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Kansas Nephrology Research Institute, LLC
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Internal Medicine Specialists, Inc
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology L.L.C
  • Michigan
    • Flint, Michigan, United States, 48504
      • Aa Mrc, Llc
    • Flint, Michigan, United States, 48532
      • Elite Research Center
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare, PLC, Troy Internal Medicine Research Division
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89129
      • Pelican Point Dialysis - DaVita Clinical Research
  • New York
    • Albany, New York, United States, 12206
      • Albany Medical College
    • Bronx, New York, United States, 10455
      • CHEAR Center LLC
    • Great Neck, New York, United States, 11021
      • North Shore University Hospital: Division of Nephrology
    • Smithtown, New York, United States, 11787
      • Endocrine Associates of Long Island, PC
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates
    • Asheville, North Carolina, United States, 28803
      • Mountain Diabetes & Endocrine Center
    • Morehead City, North Carolina, United States, 28557
      • Carteret Medical Group
    • Morehead City, North Carolina, United States, 28557
      • Diabetes and Endocrinology Consultants, P.C.
    • Rocky Mount, North Carolina, United States, 27804
      • PMG Research of Rocky Mount, LLC
    • Statesville, North Carolina, United States, 28625
      • PMG Research Inc., d/b/a PMG Research of Piedmont HealthCare
    • Wilmington, North Carolina, United States, 28401
      • Wilmington Health, PLLC
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem, LLC
  • Ohio
    • Marion, Ohio, United States, 43302
      • SV Research LLC
  • Oklahoma
    • Midwest City, Oklahoma, United States, 73130
      • Midwest Nephrology Group, PLLC
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Medical Group, Inc.
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center, LLC
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Lifespan Clinical Research Center
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • PMG Research of Charleston, LLC
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes and Endocrine Consultants
    • Chattanooga, Tennessee, United States, 37408
      • Southeast Renal Research Institute
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center, PLLC
    • Knoxville, Tennessee, United States, 37912
      • PMG Research, Inc d/b/a/ PMG Research of Knoxville
    • Knoxville, Tennessee, United States, 37938
      • PMG Research, Inc. d/b/a PMG Research of Knoxville
    • Memphis, Tennessee, United States, 38104
      • Memphis Veteran Affairs Medical Center
  • Texas
    • Arlington, Texas, United States, 76015
      • Arlington Nephrology
    • Corsicana, Texas, United States, 75110
      • Corsicana Medical Research, LLC
    • Dallas, Texas, United States, 75231
      • North Texas Endocrine Center
    • Fort Worth, Texas, United States, 76116
      • The Medical Group Of Texas
    • Houston, Texas, United States, 77024
      • PrimeCare Medical Group
    • Houston, Texas, United States, 77036
      • Mercury Clinical Research
    • Houston, Texas, United States, 77030
      • DaVita Clinical Research
    • Lewisville, Texas, United States, 75057
      • DaVita Clinical Research
    • Pearland, Texas, United States, 77584
      • Houston Methodist Research Institute - CCAT Pearland
    • San Antonio, Texas, United States, 78215
      • Clinical Advancement Center, PLLC
    • San Antonio, Texas, United States, 78154
      • Northeast Clinical Research of San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Diagnosis of type 2 diabetes mellitus (T2DM) as per local guidelines.

• Estimated glomerular filtration rate (eGFR) value calculated by central laboratory utilizing samples collected during screening and prior to enrollment of ≥ 20 mL/min/1.73 m^2 to < 60 mL/min/1.73 m^2 with albuminuria

  • eGFR and urine albumin to creatinine ratio (UACR) must meet criteria a, b, or c

    • a: eGFR (mL/min/1.73 m^2): ≥ 45 to < 60; UACR (mg/g): ≥ 600 to 5000
    • b: eGFR (mL/min/1.73 m^2): ≥ 30 to < 45; UACR (mg/g): ≥ 300 to 5000
    • c: eGFR (mL/min/1.73 m^2): ≥ 20 to < 30; UACR (mg/g): ≥ 150 to 5000

• Treatment with either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)

  • Individuals not receiving an ACEi or ARB may be enrolled if there is documented intolerance to ACEi and ARB
  • Individuals receiving less-than-maximal dose of an ACEi or ARB may be enrolled if there is a documented reason that the maximum labeled dose of ACEi and ARB could not be reached
• Individuals already receiving sodium-glucose co-transporter-2 (SGLT-2) inhibitors must be on a stable dose for at least 2 weeks prior to enrollment
• Mean systolic blood pressure (SBP) must be <160 mmHg and mean diastolic blood pressure (DBP) must be <100 mmHg
• Required baseline laboratory data, analyzed by central laboratory, within 30 days prior to enrollment

Key Exclusion Criteria:

• Hemoglobin A1c (HbA1c) > 12.0% within 30 days prior to enrollment
• Individuals with diagnosis of type 1 diabetes mellitus (T1DM) or maturity onset diabetes of the young (MODY)
• Body mass index (BMI) > 50 kg/m^2
• UACR > 5000 mg/g on any measurement during screening
• End stage kidney disease (ESKD) (i.e., chronic hemodialysis, chronic peritoneal dialysis, or history of kidney transplantation)
• Anticipated progression to ESKD (need for chronic hemodialysis, chronic peritoneal dialysis or receipt of kidney transplant) within 3 months after enrollment
• Unstable cardiovascular disease
• Pregnant or lactating females or planning to become pregnant or breastfeed during the study

• Concurrent use of either

  1. ACEi and ARB or
  2. Mineralocorticoid receptor antagonist (MRA) or direct renin inhibitor (DRI) in combination with an ACEi or ARB for at least 2 weeks prior to Enrollment
• Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the individual or impair the assessment of study results

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selonsertib; Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive SEL 18 mg for at least 48 weeks.	Drug: Placebo; Tablet administered orally once daily; Drug: SEL; Tablet administered orally once daily
Placebo Comparator: Placebo; Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive placebo-to-match SEL for at least 48 weeks.	Drug: Placebo; Tablet administered orally once daily; Drug: SEL; Tablet administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr)	The values of eGFRcr were calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation (2009). eGFRcr = 141*min(Standardized Serum Creatinine (Scr)/kappa, 1) ^alpha*max(Scr/ kappa, 1)^(-1.209)*0.993^Age*1.018[if female]*1.159[if Black], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment-specific Baselines = the average of Visits A and B values for Placebo, and the average of Visit C and Day 1 values for SEL. Visit A= enrollment, Visit B= 7-14 days after Visit A, Visit C= 21-28 days after Visit B, and Visit 1= 7-14 days after Visit C.	Treatment-specific Baselines (From enrollment (Visit A) up to 14 days after Visit A for placebo and from Visit C up to 14 days after Visit C for SEL)
eGFRcr Slope	The values of eGFRcr were calculated using the CKD-EPI Creatinine Equation (2009). eGFRcr = 141*min(Scr/kappa, 1) ^alpha*max(Scr/kappa, 1)^(-1.209)*0.993^Age*1.018[if female]*1.159[if Black], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment specific baselines for eGFRcr: average of Visit A (enrollment) and Visit B (7-14 days after Visit A) values for Placebo, and average of Visit C (21-28 days after Visit B, and Visit 1 (7-14 days after Visit C) values for SEL.	Treatment-specific Baselines through Week 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Kidney Clinical Events at Week 48	Kidney clinical events were defined as any of the following events: confirmed ≥ 40% decline in eGFRcr from baseline, or kidney failure (dialysis performed for at least 4 weeks, kidney transplantation, or confirmed decrease in eGFRcr to < 15 mL/min/1.73 m^2 for participants without dialysis or kidney transplantation), or death due to kidney disease.	Week 48
Time From Randomization to First Occurrence of a Kidney Clinical Event: Event Rate Per 100 Participant-years for First Occurrence of Kidney Clinical Event	Kidney clinical events were defined as any of the following events: confirmed ≥ 40% decline in eGFRcr from baseline, or kidney failure (dialysis performed for at least 4 weeks, kidney transplantation, or confirmed decrease in eGFRcr to < 15 mL/min/1.73 m^2 for participants without dialysis or kidney transplantation), or death due to kidney disease. This outcome measure was analyzed using event rate per 100 participant-years for first occurrence of kidney clinical event. Participant year was calculated as total follow-up duration across all participants in a given group. Follow-up duration was defined as time from Randomization to the earliest of study completion, premature study discontinuation, death, or event of interest in each row.	From randomization up to Week 101
Pre-run-in Baseline Estimated Glomerular Filtration Rate Based on Cystatin C (eGFRcys)	eGFRcys = Estimated Glomerular Filtration Rate calculated by CKD-EPI Cystatin C Equation (2012). eGFR = 133*min(Standardized Serum Cystatin (Scys)/0.8, 1) ^(-0.499)*max(Scys/0.8, 1)^(-1.328)*0.996^Age*0.932[if female]. min indicates the minimum of Scys/0.8 or 1, max indicates the maximum of Scr/0.8 or 1, and age is in years.	Pre-run-in Baseline (Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values)
eGFRcys Slope	eGFRcys = Estimated Glomerular Filtration Rate calculated by CKD-EPI Cystatin C Equation (2012). eGFR = 133*min(Scys/0.8, 1) ^(-0.499)*max(Scys/0.8, 1)^(-1.328)*0.996^Age*0.932[if female]. min indicates the minimum of Scys/0.8 or 1, max indicates the maximum of Scr/0.8 or 1, and age is in years. Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values.	Pre-run-in Baseline through Week 84

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2019
• Primary Completion (Actual): September 3, 2021
• Study Completion (Actual): September 3, 2021

Study Registration Dates

• First Submitted: July 17, 2019
• First Submitted That Met QC Criteria: July 18, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Estimate): December 21, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: GS-US-223-1017; JapicCTI-194911 (Registry Identifier: Japan Pharmaceutical Information Center); 2018-003951-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No